The invention relates to surgical adhesives, and in particular to adhesives which are formed by combination or reaction of their components (hereinafter, "activated") at the wound site.
Surgical adhesives have long been of interest for reconstructing tissues due to the ease of applicability and combined mechanical securement and sealing function. Early use of a fibrin based adhesive, while totally biodegradable, was compromised by poor adhesive strength especially over time as enzyme degradation rapidly depolymerized the fibrin. Modern forms of fibrin adhesives incorporate enzyme inhibitors not only for practical workability, but to retard in-vivo degradation and loss of strength as described in U.S. Pat. No. 4,298,598. Still, these fibrin adhesives require the mixing of two components with long reconstitution times and demonstrate limited and variable working time before setting. In addition, the use of human pooled blood in these products has raised concern regarding potential viral contamination and transmission.
Synthetic adhesive systems, such as the cyanoacrylates and cyanobutylates have high adhesive strength, but have poor degradation properties, with toxic byproducts such as formaldehyde being formed. Further, these materials are mechanically stiff and have poor integration properties with healing tissues. The cyanoacrylate type adhesive systems incorporate almost pure monomer which is initiated by water to form a high strength polymer. The rapidly setting adhesive is difficult to apply in some cases, especially in endoscopic use where the adhesive can set within the catheter lumen. Synthetic prepolymer approaches such as described in U.S. Pat. No. 4,804,691 may utilize biodegradable polymer components, but often rely on toxic components such as isocyanates and metal catalysts. Small amounts of toxicity may have adverse effect on the critical tissue to adhesive interface of a surgical adhesive.
Collagen and gelatin based adhesive solutions have been investigated. Early clinical work with the gelatin-resorcinol-formaldehyde adhesive showed problems with tissue compatibility to the chemical agents and the cumbersome preparation of the adhesive. The use of a more toxicologically compatible collagen solution as described in EPA 0466383A1 requires heating of a collagen solution to partially transform it to gelatin. When applied heated onto the tissues, the material cools to form a bond. In this case the adhesive is only held together by chain entanglement of the collagen/gelatin chains, providing limited mechanical strength which is easily disrupted during subsequent hydration and enzymatic action. Stability of the adhesive material at higher solids content was a performance limitation.
A method described in U.S. Pat. No. 5,156,613 describes the use of a solid collagen filler material which is applied to tissues while an energy source heats both the tissues and the filler material as a tissue welding aid. The denaturation of the tissues and filler, upon cooling provides a mechanical bond. While the approach utilizes high solids content adhesive, essentially a solid, the resultant adhesive material is held together by chain entanglement of the collagen/gelatin chains, limiting mechanical strength and biodegradation resistance. In addition, the inherent damage to underlying tissues of tissue welding approaches in general may prevent use on or near sensitive tissues such as fragile vasculature, nervous tissue, ocular tissue, and areas of cosmetic concern such as the face and neck. A similar approach is described in U.S. Pat. No. 5,209,776 where peptides such as collagen and albumin are mixed with either a polysaccharide or polyalcohol to form a viscous solution which can be used as a sealant or coating. As the coating has no material integrity, it is a weak flowable gel as described, with the primary utility as a adjuvant to tissue welding techniques.